Resveratrol ameliorates triglyceride accumulation through FXR deacetylation in high glucose-treated HepG2 cells

Hepatic lipid accumulation promotes the development of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. Sirt1, an NAD+-dependent histone deacetylase, plays a crucial role in NAFLD pathogenesis by regulating glycolipid metabolism. This study aims to evaluate the hepatoprotective effects and underlying mechanisms of resveratrol in T2DM-induced hepatic lipid accumulation. In vitro analysis of Sirt1 expression was conducted in high glucose (HG) -cultured HepG2 cells. It was observed that resveratrol (20 μM) significantly counteracted the triglyceride deposition and lipid droplet accumulation induced by the silencing of Sirt1. Further mechanistic studies attributed this benefit to the inhibition of FXR acetylation through upregulation of Sirt1. Notably, this hepatoprotective effect was abrogated upon the silencing of FXR. Overall, resveratrol reduced HG-induced lipid deposition by regulating the Sirt1-mediated deacetylation of FXR. The findings support the clinical potential of resveratrol in managing or preventing T2DM-induced hepatic steatosis